Context, ethics and pharmacogenetics

Most of the literature on pharmacogenetics assumes that the main problems in implementing the technology will be institutional ones (due to funding or regulation) and that although it involves genetic testing, the ethical issues involved in pharmacogenetics are different from, even less than, 'traditional' genetic testing. Very little attention has been paid to how clinicians will accept this technology, their attitudes towards it and how it will affect clinical practice. This paper presents results from interviews with clinicians who are beginning to use pharmacogenetics and explores how they view the ethics of pharmacogenetic testing, its use to exclude some patients from treatment, and how this kind of testing fits into broader debates around genetics. In particular this paper examines the attitudes of breast cancer and Alzheimer's disease specialists. The results of these interviews will be compared with the picture of pharmacogenetics painted in the published literature, as a way of rooting this somewhat speculative writing in clinical practice

Knowledge of Pharmacogenetics among Healthcare Professionals and Faculty Members of Health Training Institutions in Ghana

Background: Pharmacogenetics has a potential for optimizing drug response and identifying risk of toxicity for patients. Pharmacogenetics knowledge of healthcare professionals and the unmet need for pharmacogenetics education in health training institutions are some of the challenges of integrating pharmacogenetics into routine medical practice.Aim: To assess pharmacogenetics knowledge among healthcare professionals and faculty members of health training institutions in Ghana.Method: Semi-structured questionnaires were used to interview healthcare professionals from selected public and private hospitals. Faculty members from health training institutions were also interviewed.Results: The respondents were Medical doctors 42 (46.7%), Pharmacists 29 (32.2%) and Nurses 19 (21.1%). Healthcare professionals rated their knowledge of Pharmacogenetics as Excellent 5 (5.6%), Very Good 10 (11.2%), Good 53 (60%) and Poor 19 (21.4%). Thirty-two faculty members from health training institutions were also interviewed. Faculty members rated their knowledge of pharmacogenetics as Excellent 2 (6.3%), Very Good 3 (9.4%), Good 9 (28.1%), Fair 12 (37.5%) and Poor 6 (18.8%). Thirty seven percent (12) of these faculty members said pharmacogenetics was not part of their institutions’ curriculum, 7 (22%) did not know if pharmacogenetics was part of their curriculum and only 13 (40.6%) said it was part of their curriculum.Conclusion: Few healthcare professionals and faculty members of training institutions are aware of the discipline of pharmacogenetics. There is the need for continuous professional education on pharmacogenetics and development of competency standards for all healthcare professionals in Ghana.Keywords: Pharmacogenetics; Faculty, Curriculum, Education, Ghanaia

Pharmacogenetic testing in oncology: a Brazilian perspective

Pharmacogenetics, a major component of individualized or precision medicine, relies on human genetic diversity. The remarkable developments in sequencing technologies have revealed that the number of genetic variants modulating drug action is much higher than previously thought and that a true personalized prediction of drug response requires attention to rare mutations (minor allele frequency, MAFo1%) in addition to polymorphisms (MAF41%) in pharmacogenes. This has major implications for the conceptual development and clinical implementation of pharmacogenetics. Drugs used in cancer treatment have been major targets of pharmacogenetics studies, encompassing both germline polymorphisms and somatic variants in the tumor genome. The present overview, however, has a narrower scope and is focused on germline cancer pharmacogenetics, more specifically, on drug/gene pairs for which pharmacogenetics-informed prescription guidelines have been published by the Clinical Pharmacogenetics Implementation Consortium and/or the Dutch Pharmacogenetic Working Group, namely, thiopurines/TPMT, fluoropyrimidines/UGT1A1, irinotecan/UGT1A1 and tamoxifen/CYP2D6. I begin by reviewing the general principles of pharmacogenetics-informed prescription, pharmacogenetics testing and the perceived barriers to the adoption of routine pharmacogenetics testing in clinical practice. Then, I highlight aspects of the pharmacogenetics testing of the selected drug-gene pairs and finally present pharmacogenetics data from Brazilian studies pertinent to these drug-gene pairs. I conclude with the notion that pharmacogenetics testing has the potential to greatly benefit patients by enabling precision medicine applied to drug therapy, ensuring better efficacy and reducing the risk of adverse effects

Pharmacogenetics : the science of predictive clinical pharmacology

The study of pharmacogenetics has expanded from what were initially casual family-based clinical drug response observations, to a fully-fledged science with direct therapeutic applications, all within a time-span of less than 60 years. A wide spectrum of polymorphisms, located within several genes, are now recognised to influence the pharmacokinetics and pharmacodynamics of the majority of drugs within our therapeutic armamentarium. This information forms the basis for the new development of pharmacogenetic genotyping tests, which can be used to predict the therapeutic and/or adverse effects of a specific drug in a particular patient. Pharmacogenetic-guided, patient targeted therapy has now become the developing fulcrum of personalized medicine, as it provides the best means to optimize benefit/risk ratio in pharmacological management.peer-reviewe

Pharmacogenomic testing and its future in community pharmacy

Although it is common to see pharmacogenomic testing used North America and Australia, it is not yet part of practice in the UK. With the promise of genomic screening becoming part of the NHS, pharmacists must equip themselves with a knowledge of how the process works. Source: Shutterstock.com In January 2019, the UK government unveiled its ten-year plan for NHS England and emphasised the role pharmacists can play in promoting patient self-care[1]. There was also a focus on delivering value from medicines and reducing avoidable medicines related-harm, which costs the NHS a minimum of £98.5m per year[2]. This coincides with the NHS Genomic Medicine Service, which will be rolled out across England from April 2020, meaning that the routine use of genomic screening and personalised treatments will be the new normal in the NHS[3],[4]. Pharmacists’ advice currently relies on knowledge of observable patient characteristics, such as age, weight, comorbidities and concurrent medicines, while largely disregarding genetics. However, it is estimated that genetic factors could contribute to between 25–50% of inappropriate drug responses[5]. Knowing exactly which medicine to use for a patient and which to avoid can be a challenging task in clinical practice. However, pharmacogenomics can provide the prescriber with additional information on some of the unobserved patient characteristics that affect drug response — this can assist with both drug selection and safety. Therefore, the combination of this pharmacogenomic information along with other factors influencing pharmaceutical care may provide an opportunity to deliver more ‘personalised’ medicine, facilitating better selection and reducing the need for ‘trial and error’ prescribing

Genetic polymorphism of cytochrome p450 (2C19) enzyme in Iranian Turkman ethnic group

Objective: Different findings indicate that CYP2C plays a clinical role in determining interindividual and interethnic differences in drug effectiveness. The ethnic differences in the frequency of CYP2C19 mutant alleles continue to be a significant study topic. The aim of the present study was to assess the frequency of allelic variants of CYP2C19 in Turkman ethnic groups and compare them with the frequencies in other ethnic populations. Methods: The study group included 140 unrelated healthy ethnic Turkman subject referred to the Health Center. Genotyping of CYP2C19 alleles (CYP2C19*1, CYP2C19*2, and CYP2C19*3 alleles) was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique Results: The allele frequency of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 56.43%, 23.57% and 20%, respectively. The result also showed that 39.7% of subjects expressed the CYP2C19*1/*1 genotype. While 42.1%, 9.3%, 9.3% and 1.4% expressed CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2 and CYP2C19*3/*3 genotypes, respectively. The genotype CYP2C19*2/*3 was not expressed in this study population. The findings suggested that 10% of subjects were poor metabolizers by expressing CYP2C19*2/*2 and CYP2C19*3/*3 genotypes. Fifty one percent of subjects were intermediate metabolizers having CYP2C19*1/*2, CYP2C19*2/*3 and CYP2C19*1/*3 genotypes and 37.86% were found to be extensive metabolizers expressing CYP2C19*1/*1 genotype. The frequency of intermediate metabolizers genotype was high (51%) in Turkman ethnic groups. Conclusion: This study showed that the determined allelic variants of CYP2C19 (CYP2C19*2 and CYP2C19*3 mutations) in Turkman ethnic group are comparable to other populations. These findings could be useful for the clinicians in different country to determine optimal dosage and effectiveness of drugs metabolized by this polymorphic enzyme. © OMSB, 2013

Pharmacogenetics of analgesic drugs

• Individual variability in pain perception and differences in the efficacy of analgesic drugs are complex phenomena and are partly genetically predetermined. • Analgesics act in various ways on the peripheral and central pain pathways and are regarded as one of the most valuable but equally dangerous groups of medications. • While pharmacokinetic properties of drugs, metabolism in particular, have been scrutinised by genotype–phenotype correlation studies, the clinical significance of inherited variants in genes governing pharmacodynamics of analgesics remains largely unexplored (apart from the µ-opioid receptor). • Lack of replication of the findings from one study to another makes meaningful personalised analgesic regime still a distant future. • This narrative review will focus on findings related to pharmacogenetics of commonly used analgesic medications and highlight authors’ views on future clinical implications of pharmacogenetics in the context of pharmacological treatment of chronic pain

Individualized immunosuppression in transplant patients: potential role of pharmacogenetics.

The immunosuppressive drugs used to prevent the rejection of transplanted organs have a narrow therapeutic index. Under treatment results in episodes of rejection leading to either damage or loss of the organ. Over immunosuppression increases the risk of infection and malignancy as well as drug specific complications including diabetes mellitus and nephrotoxicity. There is wide variation in the drug dose required to achieve target blood concentrations and there is often dissociation between pharmacokinetics and pharmacodynamics. Currently, immunosuppressive drug treatment is individualized based on a clinical assessment of the risk of rejection or toxicity. Therapeutic drug monitoring is routinely employed for several immunosuppressive drugs. Pharmacogenetics has the potential to complement therapeutic drug monitoring but clinical benefit has yet to be demonstrated. Novel biomarker-based approaches to risk stratification and pharmacodynamic monitoring are under development and are ready for clinical trials

Some aspects of genetics and pharmacogenetics understanding by pharmacy students in Ukraine

Background: Prescription and administration of drugs are still carried out without taking into consideration the individual’s needs of a particular patient on the post-Soviet territory. A pharmacist may play a crucial role in the field of pharmacogenetics development in any country, nevertheless his/her role is uncertain even in the countries where pharmacogenetics is intensively developed. The aim of the present work is to analyze students’ awareness about pharmacogenetics in the National University of Pharmacy (NUPh) since its development is delayed in Ukraine.Methods: Field investigations have been used in this work. The material analysis based on questioning 637 students of the 1st–4th year majoring in pharmacy has been carried out.Results: The analysis of the future pharmacists’ awareness in the field of genetics and pharmacogenetics, as well as the study of the sex specificity of this awareness, has been carried out for the first time in Ukraine. It has been stated that more than 70% of the students questioned got the information about pharmacogenetics in University for the first time. However, only more than one-third of respondents (37.7% of males and 43.9% of females) correctly understand the idea of this discipline. About half of the students questioned thought that pharmacocorrection of hereditary diseases was impossible. It has been shown that on the whole females were more informed about pharmacogenetics than males. So, they can become more active persons of pharmaceutical market in future.Conclusion: The awareness about pharmacogenetics and its role in personalized medicine is not satisfactory both in Ukraine and other countries. Thus, it is necessary to pay more attention to the aspects of pharmacogenetics when training competent up to date specialists in the field of pharmacy. Effective development of the appropriate infrastructure in pharmacogenetics testing and its introduction among the population of Ukraine are also necessary.Keywords: Pharmacogenetics; Genetics; Personalized medicine; Pharmacy students; Ukrain

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD